In this proposal we propose to elucidate pathways and mechanisms involved with lipoprotein conversions. In particular, we will investigate the processes responsible for the formation of low density lipoproteins (LDL) from very low density lipoproteins (VLDL) and the possible contribution of the process to the high density lipoproteins (HDL). We furthermore will determine whether chylomicrons may be converted to VLDL and to LDL-like particles and whether they contribute to HDL. Our novel hypothesis is that during hipolysis of triglyceride-rich lipoproteins (chylomicrons and VLDL), residual core constituents (predominantly cholesterol esters) and surplus surface constituents (phospholipids, unesterified cholesterol and proteins) form LDL and contribute to HDL, respectively. Thus, the levels of all plasma lipoproteins may be related to rates of triglyceride transport and activities of the triglyceride hydrolyzing enzymes, the lipoprotein lipases. Our approach to elucidate these pathways is based predominantly on studies carried out in vitro and with well characterized incubation systems. Triglyceride-rich lipoproteins will be introduced to lipolytic systems and produce lipoproteins ("IDL", "LDL" and "HDL") will be isolated and characterized. Special attention will be given to the structure of the product lipoproteins. A complete characterization will include determinations of lipid composition, apoprotein composition, flotation properties, size, shape and organization of core constituents and surface constituents of the lipoproteins. To carry out the study we have developed during the last few years methods and procedures necessary to obtain reliable and meaningful answers to the above questions. These are described in detail in the Research Plan section of the proposal. Our aim is to use these methods and procedures for the assessment of the effects of the following factors on the formation of LDL-like and HDL-like particles: A. lipoprotein lipase, B. the triglyceride hydrolase of hepatic origin, C. plasma proteins and lipoproteins, D. the lecithin:cholesterol acyltransferase (LCAT), E. tissue and endothelial cells, F. liver cells.